Decreased transcription of the sodium-phosphate transporter gene in the hypophosphatemic mouse

Abstract

Recently, it has been hypothesized that the proximal tubular Na(+)-Pi transporter may play a role in murine X-linked hypophosphatemic vitamin D-resistant rickets. In the present investigation, Western blot analysis of renal brush-border membrane proteins, utilizing polyclonal antisera raised against the mouse Na(+)-Pi transporter, revealed a predominant band at 87 kDa in normal and hypophosphatemic (Hyp) mice. The intensity of this band was reduced in the Hyp mouse by 4.5-fold (Hyp/normal = 0.22 +/- 0.04, n = 3, P < 0.05). Additionally, immunohistochemical analysis of kidney cortex in both mice localized the protein to the apical membrane of the proximal tubules. Relative transcription rates of the Na(+)-Pi transporter gene in the normal and Hyp mouse were then investigated. Nuclear run-on assays showed a 51 +/- 0.02% decreased rate of transcription of the Na(+)-Pi transporter gene in the Hyp mice (n = 3). Thus abnormal transcriptional control of this gene in the Hyp mouse likely plays a role in X-linked hypophosphatemia.